The goal of this proposal is to better understand the mechanisms underlying synaptic transmission. We will study the unc-13 gene in Caenorhabditis elegans to determine its role in regulating neurotransmitter release. First, we will examine alterations in the cellular and subcellular localization of UNC-13 in mutants with defects in neurotransmission using indirect immunofluorescence. Using antibodies which recognize UNC-13 and other proteins important for synaptic transmission, we will show the localization of UNC-13 relative to other presynaptic proteins. To further investigate how unc-13 is involved in neurotransmitter release, we will search for protein-protein interactions between UNC-13 and other proteins using both extragenic suppressor screens and the two-hybrid system in yeast. While this is basic research, it is clearly relevant to health. Proper neurotransmitter release is crucial to proper function of the nervous system, and defective neurotransmitter release has been implicated in many psychiatric and neurobiological disorders.